Since you mention pain several times, one pretty significant gap in this discussion is consideration of the dissociation between the sensory and affective components of pain experience. The reported intensity of pain is correlated with the reported unpleasantness of pain, but the two components can be pushed in opposite directions (for example, reported pain intensity can remain constant while pain unpleasantness is increased or decreased). The affective component of pain is presumably what matters morally, and valance is definitionally part of the affective component.
This is important because a lot of your discussion of pain is referencing the reported sensory intensity of pain. For example, the gamma band oscillations appear to be tracking the sensory component of pain (the Yue et al article traces it to the primary somatosensory cortex). This would suggest that even if these oscillations are relatively predictive of pain, they are not good candidates for biomarkers that could be used to tell us something about the moral status of other species, since they occur upstream of the neural activity connected to affect.
So they include the prefrontal cortex, too, for second order appraisals. They also point to (the posterior sector of) ACC area 24, specifically, in the text.
Micheal, the link between specific brain regions and encoding pain affect is pretty complicated and controversial, as mentioned in the original article. So I would first note that even if we don’t know exactly what specific brain regions are doing, there’s still a lot of evidence (including several lines of evidence cited in the Price article you mention) for a sensory/affective dissociation.
That said, the brain regions most commonly linked to the affective dimension of pain are the anterior cingulate cortex (with some controversy as to whether the relevant region should be referred to as part of the midcingulate rather than the ACC), and the insula cortex (possibly along with the neighboring parietal operculum). But there was also a really impressively thorough recent study by Corder et a that seemed to show that the basolateral amygdala plays a central role in the unpleasantness of pain: https://science.sciencemag.org/content/363/6424/276 .
One difficulty with all of these regions is that they’re involved in many different cognitive processes, so it’s hard to suss out exactly what role is being played in pain. Part of what was especially cool about the Corder study was that it drilled down to specific neural ensembles within the amgdala that really did seem to play a pain-specific role. Similarly, more fine-grained examinations of the cingulate have helped to clarify which regions are involved in pain vs other processes: https://www.sciencedirect.com/science/article/abs/pii/S0891061815300326 and see also: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801068/ ). The most detailed argument for a central role of the insula in pain affect is Grahek’s book Feeling Pain and Being in Pain, which is a bit dated now, but there’s still a lot of emphasis on the insula as a key area for pain’s unpleasantness. In humans, there’s evidence that lesions to the cingulate and insula can selectively impair pain affect while preserving pain sensation, direct stimulation of the insula can cause expressions of pain, and deep brain stimulation on the cingulate has selectively lessened the affective component of chronic pain in early studies.
So I guess the tl/dr is that the regions most likely to play a central role in pain affect are the anterior midcingulate cortex (which is the region Price referred to as the posterior ACC), the posterior insula and parietal operculum, and (specific neuronal ensambles in) the basolateral amygdala, but there are also a lot of really big questions remaining.
Thanks for your comment! I agree that the distinction between the sensory and affective components of pain experience is an important one that merits more discussion. I briefly considered including such a discussion, but the report was already long and I was hoping to avoid adding another layer of complexity. My assumption was that, while it’s possible for the two components to come apart, such dissociation is rare enough that we can safely ignore it at this level of abstraction. That could be a naïve assumption, though. Even if not, you’re right that by failing to take account of the different components, I’ve introduced an ambiguity into the report. When I refer to the intensity of pain, I intend to refer to the degree of felt badness of the experience (that is, the affective component). But the sensory component can also be said to be more or less intense, and some of the literature I cite either conflates the two components or refers to sensory intensity.
I would be interested to hear more of your thoughts about the Yue article and related work. Suppose it’s true that gamma-band oscillations reliably track the sensory intensity of pain experience and that for our purposes the sensory component is morally irrelevant. If sensory intensity and affective intensity are correlated in humans, do you think it’s reasonable to assume that the components are correlated in other mammals? If so, then we can still use gamma-band oscillations as a rough proxy for the thing we care about, at least in animals neurologically similar to humans.
Basically, my main questions are:
(1) How often and under what conditions does sensory intensity come apart from affective intensity in humans?
(2) How can we use what we know about the components coming apart in humans to predict how often and under what conditions sensory intensity and affective intensity come apart in nonhuman animals?
If you’re interested, I’d love to schedule a call to talk further. This might be too big a topic to discuss easily via Forum comments.
Jason, thanks for the response! I’d definitely be interested in talking more some time...I’m a bit of a novice on this forum so let me know the best way to set something up.
I think for (1), it depends on how strongly you mean “comes apart.” If we just mean varying one dimension while the other stays constant, or varying one dimension more than the other, there are a huge number of instances where this occurs. If, however, you mean the stronger case of “coming apart” where one dimension is present while the other is completely absent, the evidence is a bit more controversial. Lesion studies like cingulotomies and pain asymbolia cases (resulting from insula lesions) are often cited as examples, but some argue that cingulotomies don’t produce true dissociations and the pain asymbolia cases are pretty rare and a bit strange in other ways. Morphine or other opioids are sometimes said to eliminate pain affect without eliminating pain sensation, but again there are scholars who disagree with that interpretation. There are also many other forms of studies (such as direct stimulation, transcranial magnetic stimulation, deep brain stimulation) that are able to produce differential effects for pain affect and pain sensation, but I don’t think any of them have resulted in complete dissociations.
Regarding (2), I argued in the above chapter that we need better research into the nonverbal effects of sensory-affective dissociation in humans. A lot of the research on the unpleasantness of pain in humans relies too much on verbal self-report, which makes it difficult to know how to map this dimension to other animals (conditioned place aversion is currently one of the ways of trying to test pain affect).
Finally, you also asked:: “If sensory intensity and affective intensity are correlated in humans, do you think it’s reasonable to assume that the components are correlated in other mammals?”
So the typical pain signal in humans might follow roughly this pattern: a noxious stimulus causes activity in nociceptors in the peripheral nervous system, which then send a signal to the spinal cord, which transmits information to the thalamus, which then passes the info on to sensory cortical regions and to affective regions (and there are some direct connections between the thalamus and affective regions). I think the magnitude at every step in that process is pretty strongly correlated with the ultimate affective intensity. But we wouldn’t want to say activity in nociceptors is a biomarker for valences experience despite the fact that it is strongly correlated with it, because we know of many instances where nociceptive activity can come apart from experienced pain. Granted, the connection between the sensory dimension of pain is more strongly correlated with experienced unpleasantness, but it seems like the same problem exists. So I guess I just tend to think that “X is a neurobiological marker of Y” requires something stronger than “X is highly correlated with/and or predictive of Y.”
To take one example of why this could matter, an expectation of pain can influence pain unpleasantness more than pain intensity ratings. So if you were using a marker that only predicted pain intensity, you could miss important details about the actual welfare implications of the pains. Many of the pains that occur in agricultural animals or laboratory animals presumably occur in situations where differential influences (such as that from anticipated pain, high anxiety, depression, etc) on the affective components of pain could be important.
Great, this is fantastic, thanks! Clearly there is a lot more I need to think about! I just sent you a message to arrange a chat. For anyone following this exchange, I’ll try to post some more thoughts on this topic after Adam and I have talked.
Since you mention pain several times, one pretty significant gap in this discussion is consideration of the dissociation between the sensory and affective components of pain experience. The reported intensity of pain is correlated with the reported unpleasantness of pain, but the two components can be pushed in opposite directions (for example, reported pain intensity can remain constant while pain unpleasantness is increased or decreased). The affective component of pain is presumably what matters morally, and valance is definitionally part of the affective component.
This is important because a lot of your discussion of pain is referencing the reported sensory intensity of pain. For example, the gamma band oscillations appear to be tracking the sensory component of pain (the Yue et al article traces it to the primary somatosensory cortex). This would suggest that even if these oscillations are relatively predictive of pain, they are not good candidates for biomarkers that could be used to tell us something about the moral status of other species, since they occur upstream of the neural activity connected to affect.
Hi Adam, where are the right places to look for the affective component? I see the anterior cingulate cortex (ACC) discussed in a few places, e.g. its relationship with pain on wiki page for the ACC. They cite Price, D. D. (2000). Psychological and neural mechanisms of the affective dimension of pain. Science, 288(5472), 1769-1772, and that article includes this figure for the neural pathway of pain:
So they include the prefrontal cortex, too, for second order appraisals. They also point to (the posterior sector of) ACC area 24, specifically, in the text.
It seems the ACC is involved in both social rejection and physical pain in humans, and emotional contagion in mice (and spike counts in area 24 were correlated with intensity), too.
Are there more specific regions or other regions we should look to that you’re aware of?
Micheal, the link between specific brain regions and encoding pain affect is pretty complicated and controversial, as mentioned in the original article. So I would first note that even if we don’t know exactly what specific brain regions are doing, there’s still a lot of evidence (including several lines of evidence cited in the Price article you mention) for a sensory/affective dissociation.
That said, the brain regions most commonly linked to the affective dimension of pain are the anterior cingulate cortex (with some controversy as to whether the relevant region should be referred to as part of the midcingulate rather than the ACC), and the insula cortex (possibly along with the neighboring parietal operculum). But there was also a really impressively thorough recent study by Corder et a that seemed to show that the basolateral amygdala plays a central role in the unpleasantness of pain: https://science.sciencemag.org/content/363/6424/276 .
One difficulty with all of these regions is that they’re involved in many different cognitive processes, so it’s hard to suss out exactly what role is being played in pain. Part of what was especially cool about the Corder study was that it drilled down to specific neural ensembles within the amgdala that really did seem to play a pain-specific role. Similarly, more fine-grained examinations of the cingulate have helped to clarify which regions are involved in pain vs other processes: https://www.sciencedirect.com/science/article/abs/pii/S0891061815300326 and see also: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801068/ ). The most detailed argument for a central role of the insula in pain affect is Grahek’s book Feeling Pain and Being in Pain, which is a bit dated now, but there’s still a lot of emphasis on the insula as a key area for pain’s unpleasantness. In humans, there’s evidence that lesions to the cingulate and insula can selectively impair pain affect while preserving pain sensation, direct stimulation of the insula can cause expressions of pain, and deep brain stimulation on the cingulate has selectively lessened the affective component of chronic pain in early studies.
So I guess the tl/dr is that the regions most likely to play a central role in pain affect are the anterior midcingulate cortex (which is the region Price referred to as the posterior ACC), the posterior insula and parietal operculum, and (specific neuronal ensambles in) the basolateral amygdala, but there are also a lot of really big questions remaining.
Hey Adam,
Thanks for your comment! I agree that the distinction between the sensory and affective components of pain experience is an important one that merits more discussion. I briefly considered including such a discussion, but the report was already long and I was hoping to avoid adding another layer of complexity. My assumption was that, while it’s possible for the two components to come apart, such dissociation is rare enough that we can safely ignore it at this level of abstraction. That could be a naïve assumption, though. Even if not, you’re right that by failing to take account of the different components, I’ve introduced an ambiguity into the report. When I refer to the intensity of pain, I intend to refer to the degree of felt badness of the experience (that is, the affective component). But the sensory component can also be said to be more or less intense, and some of the literature I cite either conflates the two components or refers to sensory intensity.
I would be interested to hear more of your thoughts about the Yue article and related work. Suppose it’s true that gamma-band oscillations reliably track the sensory intensity of pain experience and that for our purposes the sensory component is morally irrelevant. If sensory intensity and affective intensity are correlated in humans, do you think it’s reasonable to assume that the components are correlated in other mammals? If so, then we can still use gamma-band oscillations as a rough proxy for the thing we care about, at least in animals neurologically similar to humans.
Basically, my main questions are:
(1) How often and under what conditions does sensory intensity come apart from affective intensity in humans? (2) How can we use what we know about the components coming apart in humans to predict how often and under what conditions sensory intensity and affective intensity come apart in nonhuman animals?
If you’re interested, I’d love to schedule a call to talk further. This might be too big a topic to discuss easily via Forum comments.
Jason, thanks for the response! I’d definitely be interested in talking more some time...I’m a bit of a novice on this forum so let me know the best way to set something up.
As a first pass at your questions, my chapter The Unpleasantness of Pain for Humans and Other Animals gets at some of them.
I think for (1), it depends on how strongly you mean “comes apart.” If we just mean varying one dimension while the other stays constant, or varying one dimension more than the other, there are a huge number of instances where this occurs. If, however, you mean the stronger case of “coming apart” where one dimension is present while the other is completely absent, the evidence is a bit more controversial. Lesion studies like cingulotomies and pain asymbolia cases (resulting from insula lesions) are often cited as examples, but some argue that cingulotomies don’t produce true dissociations and the pain asymbolia cases are pretty rare and a bit strange in other ways. Morphine or other opioids are sometimes said to eliminate pain affect without eliminating pain sensation, but again there are scholars who disagree with that interpretation. There are also many other forms of studies (such as direct stimulation, transcranial magnetic stimulation, deep brain stimulation) that are able to produce differential effects for pain affect and pain sensation, but I don’t think any of them have resulted in complete dissociations.
Regarding (2), I argued in the above chapter that we need better research into the nonverbal effects of sensory-affective dissociation in humans. A lot of the research on the unpleasantness of pain in humans relies too much on verbal self-report, which makes it difficult to know how to map this dimension to other animals (conditioned place aversion is currently one of the ways of trying to test pain affect).
Finally, you also asked:: “If sensory intensity and affective intensity are correlated in humans, do you think it’s reasonable to assume that the components are correlated in other mammals?”
So the typical pain signal in humans might follow roughly this pattern: a noxious stimulus causes activity in nociceptors in the peripheral nervous system, which then send a signal to the spinal cord, which transmits information to the thalamus, which then passes the info on to sensory cortical regions and to affective regions (and there are some direct connections between the thalamus and affective regions). I think the magnitude at every step in that process is pretty strongly correlated with the ultimate affective intensity. But we wouldn’t want to say activity in nociceptors is a biomarker for valences experience despite the fact that it is strongly correlated with it, because we know of many instances where nociceptive activity can come apart from experienced pain. Granted, the connection between the sensory dimension of pain is more strongly correlated with experienced unpleasantness, but it seems like the same problem exists. So I guess I just tend to think that “X is a neurobiological marker of Y” requires something stronger than “X is highly correlated with/and or predictive of Y.”
To take one example of why this could matter, an expectation of pain can influence pain unpleasantness more than pain intensity ratings. So if you were using a marker that only predicted pain intensity, you could miss important details about the actual welfare implications of the pains. Many of the pains that occur in agricultural animals or laboratory animals presumably occur in situations where differential influences (such as that from anticipated pain, high anxiety, depression, etc) on the affective components of pain could be important.
Great, this is fantastic, thanks! Clearly there is a lot more I need to think about! I just sent you a message to arrange a chat. For anyone following this exchange, I’ll try to post some more thoughts on this topic after Adam and I have talked.